Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA.
Science. 2022 Apr 22;376(6591):410-416. doi: 10.1126/science.abo0039. Epub 2022 Apr 21.
Cross-electrophile coupling (XEC) reactions of aryl and alkyl electrophiles are appealing but limited to specific substrate classes. Here, we report electroreductive XEC of previously incompatible electrophiles including tertiary alkyl bromides, aryl chlorides, and aryl/vinyl triflates. Reactions rely on the merger of an electrochemically active complex that selectively reacts with alkyl bromides through 1e processes and an electrochemically inactive Ni(phosphine) complex that selectively reacts with aryl electrophiles through 2e processes. Accessing Ni(phosphine) intermediates is critical to the strategy but is often challenging. We uncover a previously unknown pathway for electrochemically generating these key complexes at mild potentials through a choreographed series of ligand-exchange reactions. The mild methodology is applied to the alkylation of a range of substrates including natural products and pharmaceuticals.
交叉亲电偶联（XEC）反应的芳基和烷基亲电试剂很有吸引力，但仅限于特定的底物类别。在这里，我们报告了以前不兼容的亲电试剂的电还原 XEC，包括叔烷基溴、芳基氯和芳基/乙烯基三氟甲磺酸酯。反应依赖于电化学活性配合物的合并，该配合物通过 1e 过程选择性地与烷基溴反应，而电化学惰性的 Ni（膦）配合物通过 2e 过程选择性地与芳基亲电试剂反应。获得 Ni（膦）中间体对于该策略至关重要，但通常具有挑战性。我们通过一系列精心设计的配体交换反应揭示了一种以前未知的途径，可在温和的电位下电化学生成这些关键配合物。温和的方法学适用于一系列底物的烷基化，包括天然产物和药物。
